Fluid plug for sterile processes and methods of using the same

ABSTRACT

A fluid plug for use with sterile processes such as the manufacture or production of pharmaceuticals and biologics is disclosed. The fluid plug is made of a material or materials that will tolerate sterilizing processes such as gamma irradiation. The fluid plug is used to selectively plug the ends of flexible polymer conduits that may be connected to fluids, reagents, or products used or generated as part of the manufacturing process. Also disclosed is the use of the plugs in combination with a series of valves in a block-and-bleed arrangement to enable the sterile transfer and connection of fluids, reagents, or products within a process flow.

RELATED APPLICATION

This Application claims priority to U.S. Provisional Patent ApplicationNo. 62/201,044 filed on Aug. 4, 2015, which is hereby incorporated byreference in its entirety. Priority is claimed pursuant to 35 U.S.C. §119 and any other applicable statute.

FIELD OF THE INVENTION

The field of the invention generally relates to plugs that are used inconnection with connectors, valves, or interfaces used by pharmaceuticaland biological applications or other hygienic process industries.

BACKGROUND

Many commercial products are produced using chemical as well asbiological processes. Pharmaceuticals, for example, are produced incommercial quantities using scaled-up reactors and other equipment.So-called biologics are drugs or other compounds that are produced orisolated from living entities such as cells or tissue. Biologics can becomposed of proteins, nucleic acids, or complex combinations of thesesubstances. They may even include living entities such as cells. Inorder to produce biologics on a commercial scale, sophisticated andexpensive equipment is needed. In both pharmaceutical and biologics, forexample, various processes need to occur before the final product isobtained. For example, in the case of biologics, cells may be grown in agrowth chamber or the like and nutrients may need to be carefullymodulated into the growth chamber. Waste products produced by cells mayalso have to be removed on a controlled basis from the fermentationchamber. As another example, biologic products produced by living cellsor other organisms may need to be extracted and concentrated. Thisprocess may involve a variety of filtration and separation techniques.

Because there are a number of individual processes required to beproduce the final product, various reactants, solutions, and washes areoften pumped or otherwise transported to various subsystems usingconduits and associated valves. These systems may be quite cumbersomeand organizationally complex due to the large numbers of conduits,valves, sensors, and the like that may be needed in such systems. Notonly are these systems visually complex (e.g., resembling spaghetti)they also include many components that are required to be sterilizedbetween uses to avoid cross-contamination issues. Indeed, the case ofdrug and biologic preparation, the Federal Food and Drug Administration(FDA) is becoming increasingly strict on cleaning, sterilization orbio-burden reduction procedures that are required for drug andpharmaceutical preparations. This is particularly of a concern becausemany of these products are produced in batches which would requirerepeated cleaning, sterilization or bio-burden reduction activities on avariety of components.

During the manufacturing process of pharmaceuticals and biologicssterile solutions and reagents are used. These sterile solutions andreagents need to be integrated into the manufacturing process in amanner that maintains the sterile nature of the reagents without anychance of introducing contaminants into the system when the reagents arecoupled to the larger production system. There is a need for devices andsystems that can be used to for the preparation and use of suchsolutions and reagents that maintains their sterile integrity or canotherwise be subject to cleaning or disinfectant operations to sterilizethe same. Preferably these devices and systems and be used withconventional sterilization modalities such gamma irradiation.

SUMMARY

A fluid plug for use with sterile processes such as the manufacture orproduction of pharmaceuticals and/or biologics, and food or dairyapplications is disclosed. The fluid plug is made of materials that willtolerate sterilizing processes such as gamma irradiation. The fluid plugis used to selectively plug the ends of flexible polymer conduits thatmay be connected to fluids, reagents, or products used or generated aspart of the manufacturing process. Also disclosed is the use of theplugs in combination with a series of valves in a block-and-bleedarrangement to enable the sterile transfer and connection of fluids,reagents, or products within a process flow.

In one embodiment, a sterile fluid system is disclosed that includes acontainer for holding fluid therein and a flexible polymer conduithaving first and second ends, the flexible polymer conduit coupled tothe container at the first end. A removable plug is configured to insertinto the second end of the flexible polymer conduit. The removable plugincludes a cap, a shank portion extending from the cap, a flexible ringdisposed along a portion of the shank, and a lever mounted on the capand configured to shorten the shank upon actuation, wherein actuation ofthe lever causes radial expansion of the flexible ring and forms afluidic seal with an interior surface of the flexible polymer conduit.

In another embodiment, a removable plug that is configured to insertinto an end of a flexible polymer conduit is disclosed. The removableplug includes a cap, a shank portion extending from the cap, a flexiblering disposed along a portion of the shank, and a lever mounted on thecap and configured to shorten the shank upon actuation, whereinactuation of the lever causes radial expansion of the flexible ring andforms a fluidic seal with an interior surface of the flexible polymerconduit, wherein the removable plug is formed from materials thattolerate gamma irradiation.

In still another embodiment, a method of connecting a fluid container toa secondary conduit in a sterile manner includes sterilizing the fluidcontainer and a first conduit connected to the fluid container, whereinthe first conduit includes a main conduit and branch conduit and whereinan end of the branch conduit and an end of the main conduit each containa removable plug therein. A first valve body is secured around the mainconduit and the branch conduit of the first conduit, wherein the firstvalve body includes a first valve for the main conduit and second valvefor the branch conduit. The first valve of the first valve body is thenclosed along with the second valve of the first valve body. The plugsare removed from the branch conduit and main conduit of the firstconduit. A second valve body is secured around a secondary conduit, thesecondary conduit having a main conduit and a branch conduit, whereinthe second valve body includes a first valve for the main conduit andsecond valve for the branch conduit of the secondary conduit. The outputof the main conduit of the first conduit is fluidically coupled (e.g.,directly or indirectly using another conduit or the like) to the mainconduit of the secondary conduit. The second valve of the first valvebody is opened along with second valve of the second valve body. Asterilant is then flowed through a fluid pathway connecting between thebranch channel of the first conduit and the branch channel of thesecondary conduit. The second valve of the first valve body and thesecond valve of the second valve body are then closed. The first valveof the first valve body and the first valve of the second valve body arethen opened to permit flow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A illustrates a plug according to one embodiment with the plug inan open state.

FIG. 1B illustrates the plug of FIG. 1A with the plug in the closedstate.

FIG. 2 illustrates a cross-sectional view of a removable plug insertedinto an end of a conduit with the lever actuated with the plug in aclosed state.

FIG. 3A illustrates a container (e.g., bag) connected to a conduit thatterminates in a valve body having two plugs inserted into the conduit(plugs inserted at end of main and end of branch conduit).

FIG. 3B illustrates a side view of the valve body according to oneembodiment. In this embodiment, the conduit is encapsulated by atwo-piece valve body. The valve body has two valves (one for mainconduit and one for branch conduit). Plugs are illustrated insertedinto, respectively, the ends of the main conduit and branch conduit.

FIGS. 4A-4E illustrate one method of using the removable plugs in ablock-and-bleed arrangement to aseptically connect or transfer afluid-containing container or the like to another conduit. The otherconduit may be connected to another source of fluid or the conduit maybe part of a biological or pharmaceutical manufacturing process.

FIG. 5 illustrates one illustrative example of a two-piece valve body aswell as an associated exoskeleton or external jacket that is used tocover a conduit that is placed within the two-piece valve body.

DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS

FIGS. 1A and 1B illustrate a plug 10 according to one embodiment. Theplug 10 includes a cap 12 and an elongate shank portion 14 that extendsgenerally perpendicular with respect to the cap 12. A lever 16 isdisposed atop the cap 12 and as explained herein, is used to adjustlength of the shank portion 14 during actuation to cause a ring 17 madefrom a flexible material to expand outward (i.e., radially with respectto long axis of shank portion 14). The outward expansion of the ring 17is caused by the compression of the ring 17 along the direction of theshank portion 14 during actuation of the lever 16 as described below.When placed in an end of a conduit 18, the expansion of the ring 17 inthe outward direction causes the ring 17 to contact an inner surface ofa conduit 18 (as seen in FIG. 2) in which the plug 10 is placed to forma fluidic seal and prevent the passage of fluid. Conversely, after theplug 10 inserted into the conduit 18 and secured to an inner surface,the lever 16 can be actuated in the reverse direction to cause ring 17to contract inwardly and away from the inner surface of the conduit 18.The plug 10 can now be removed from the conduit 18. Importantly, thisprovides for the damage-free removal of the plug 10 from the conduit 18.This is unlike, for example, barbed ends that, when removed, may affectthe shape and size of the internal surface of the conduit 18. The plugs10 described herein can be used to make selective (sealing) contact withthe inner surface of the conduit 18 without any damage.

The elongate shank portion 14 includes an extension or portion 20 thatprojects from the cap 12 and is fixed relative to the cap 12. Theextension 20 includes a flange or abutment 22 at the end that contactswith or is secured to one end of the ring 17. A moveable shaft 24 islocated inside the extension 20 and extends through the interior of thering 17 and terminates or otherwise connects to a containment flange orabutment 26 that is located on and extends from an opposing side of thering 17 (e.g., this forms a moveable portion of the shank portion 14).The ring 17 may be bonded or secured to the containment flange orabutment 26. In this regard, the ring 17 is sandwiched between theflange/abutment 22 of the extension 20 and the moveable containmentflange/abutment 26 on the shaft 24. Still referring to FIG. 1A, themoveable shaft 24 extends through the cap 12 and is connected to thelever 16. Note that a separate linkage or hinge may be used between thelever 16 and the shaft 24 instead of a direct connection. The lever 16includes a lower cam surface 28 that contacts the upper surface of thecap 12. The lower cam surface 28 may be in the configuration as a saddleas illustrated in FIGS. 1A and 1B. Rotation (e.g., actuation) of thelever 16 as seen in FIG. 1B causes the lever to rotate about the lowercam surface 28 and the shaft 24 is pulled upward in the direction ofarrow A. The shank portion 14 thus shortens in length and thecontainment flange/abutment 26 compresses the ring 17 against thestationary flange/abutment 22 and causes the ring 17 to bulge outward inthe radial direction of arrows B of FIG. 1B. The outward bulging of thering 17 will cause the exterior surface of the ring 17 to contact aninner surface of the conduit 18 (FIG. 2) in which the plug 10 is placedto form a fluidic seal. Sufficient frictional contact is made betweenthe bulging ring 17 and the inner surface of the conduit 18 such thatfluid cannot pass to the other side of the ring 17 thereby making afluidic seal.

The components of the plug 10 should be made from materials that aresuitable for sterilization processes typically used in biological andpharmaceutical applications including but not limited to irradiation(i.e., gamma irradiation). The components of the plug may be made frompolymer materials such as silicone. Materials may also include standardthermoplastics and polyolefins such as polyethylene (PE) andpolypropylene (PP) or a hard plastic such as polyetherimide (PEI) suchas ULTEM resins, polycarbonate, and polysulfones (PSU). The ring 17 ispreferably formed from a deformable polymer material such as, forexample, rubber or silicone.

FIGS. 3A and 3B illustrate the use of plugs 10 according to oneembodiment. In this embodiment, a bag, container, or the like 40 isillustrated that contains fluid therein. The fluid may contain reagents,products, or other process components in fluidic form. The bag 40 isconnected to a conduit 18 that includes at one end a valve body 42. Inthis embodiment, the valve body 42 includes two valves 44, 46. Theconduit 18 includes a main conduit 18 a and a branch conduit 18 b. Afirst valve 44 is used to control flow within the main conduit 18 awhile the second valve 46 is used to control flow within the branchconduit 18. The valve body 42 may include any number of types of valvebodies. For example, according to one embodiment and as explained infurther detail below, the valve body 42 includes an exoskeleton typevalve body in which the conduit 18 is flexible (e.g., silicone) andcontained within a hardened jacket or housing that may be opened andclosed (e.g., valve housing has first and second hinged halves 42 a and42 b as seen in FIG. 3B that can be opened and closed around the conduit18; see also FIG. 5). The actual valves 44, 46 used in the valve body 42may be manually controlled valves or automatically controlled valves(e.g., pneumatic-based or solenoid based valves). The valves 44, 46 arepinch valves in that actuation of the valve 44, 46 causes an actuatorelement to pinch (or not pinch) the flexible conduit 18. The valve 44,46 is thus able to stop flow by pinching the flexible conduit 18 or,conversely, allow flow by not pinching the flexible conduit 18. FIG. 5illustrates two such actuator elements 66 that are used to pinch theflexible conduit 18.

Referring to FIGS. 3A and 3B, two plugs 10 are inserted into terminalends of the conduit 18. One plug 10 is used to close the main conduit 18a while another plug 10 is used to close the branch conduit 18 b. In oneaspect of the invention, the bag or container 40, conduit 18, and plugs10 are subject to irradiation such as, for example, gamma irradiation.For example, without the valve body 42 being attached, the entireapparatus is placed in gamma irradiation device and irradiated to ensuresterility. After being subject to irradiation, the valve body 42 may beopened and the conduits 18 a, 18 b placed within the respective housinghalves 42 a, 42 b and the valve body 42 may be closed about theperiphery of the conduits 18 a, 18 b. The valve body 42 may include oneor more fasteners such as the threaded latch 56 of FIG. 5 to close therespective halves 42 a, 42 b (The plugs 10 maintain the sterility of thesystem after irradiation. FIG. 3B illustrates the valve body halves 42a, 42 b closed around the conduits 18 a, 18 b.

FIGS. 4A-4E illustrate how the plugs 10, 10′ are used according toanother embodiment. In this embodiment, the plugs 10, 10′ are used to,for example, to transport and connect different process aspects in asterile or aseptic manner. With reference to FIG. 4A, a bag or othercontainer 40 is connected via a conduit 18 to a valve body 42 aspreviously described in FIGS. 3A and 3B. In this particular example, themain conduit 18 a of the valve body 42 is connected to the main conduit18′ (e.g., receiving conduit) of another bag or container 40′ that hasits own valve body 42′ using an optional conduit segment 48. As seen inFIG. 4A, plugs 10, 10′ are used to close the main conduits 18 a, 18 a′and the branch conduits 18 b, 18 b′ in both conduit lines 18, 18′. Thismaintains sterile or aseptic conditions within each respective system.Next, as seen in FIG. 4B, the valves 44, 46 and 44′, 46′ of therespective valve bodies 42, 42′ are closed (if not already closed) andthe plugs 10, 10′ are removed. The respective main conduits 18 a, 18 a′are connected to one another using a conduit segment 48. The conduitsegment 48 may be connected to respective ends of the main conduits 18a, 18 a′ using a clamp 50 or the like. Note that the conduit segment 48may be jacketed with a rigid housing or exoskeleton in some embodimentsas is illustrated in FIG. 5 (e.g., where the fluid is pressurized).

With reference to FIG. 4C, a sterilant 52 is then introduced into thepathway formed between the two branch conduits 18 b, 18 b′ by openingvalves 46, 46′. The sterilant 52 may include steam, a chemical agent,ozone, or the like. Arrows A in FIG. 4C illustrate the flow direction ofthe sterilant 52 although the direction may be reversed. Aftersufficient time has elapsed, the flow of sterilant 52 is stopped. Asseen in FIG. 4D, the valves 46, 46′ are then closed and the remainingvalves 44, 44′ are opened. A sterile or aseptic connection is nowachieved. Fluid, reagents, products, and the like can now be transferredor fed from one location to another in an aseptic manner. The plugs 10,10′ were necessary to maintain component sterility prior to theconnection being made. While FIGS. 4A-4D illustrate different bags orcontainers 40, 40′ being connected, the same process may be used toconnect one bag or container 40 to any other connection as part of themanufacturing process as is illustrated in FIG. 4E. For example, in manybio and pharmaceutical processes reagents or products may need to beswapped in or out of a manufacturing process. The process outlined inFIGS. 4A-4E can be used in another number of scenarios. The plugs 10,10′ that are used ensured component sterility and may be disposed ofafter use. In the configuration of FIGS. 4A-4E, the valve bodies 42, 42′are arranged in a block-and-bleed arrangement.

FIG. 5 illustrates one embodiment of a valve body 42 according to oneembodiment. In this embodiment, there is a two-part valve body 42(illustrated in the open configuration in FIG. 5) that includes a firsthalf 42 a and a second half 42 b that are connected via a hinge 43. Eachof the first half 42 a and the second half 42 b of the valve body 42includes respective semi-circular shaped inner surface that defines apassageway through the valve body 42 when the valve body 42 is in theclosed state. In this particular example, the semi-circular shaped innersurfaces define a tee-shaped passageway although different shapedpassageways are contemplated. The semi-circular shaped inner surfacescombine to form a circular-shaped inner surface that snugly holds thecircular shaped conduit 18.

Still referring to FIG. 5, the valve body 42 includes a fastener 54 thatis used to maintain the valve body 42 in a closed state and can be usedto selectively open the valve body 42 as needed. In this example, thefastener 54 includes a threaded latch 56 element that is pivotably heldin the valve body half 42 b and a knob 58 is used to tighten or loosenthe latch 56 in place with respect to the second valve body half 42 athat includes a notch for receiving the latch 56. The valve body 42 maybe made from a number of materials. For example, the valve body 42 maybe made of a metal such as stainless steel. Alternatively, the valvebody 42 may be made from a polymer material such as acrylonitrilebutadiene styrene (ABS) or other engineered thermoplastic materialssuitable for the environment or application. Examples includepolyetherimide (PEI), aliphatic polyamides (e.g., Nylon),polyphenylsulfone (e.g., RADEL), etc.

As seen in FIG. 5, the valve body 42 has terminating flanges 60, 62, 64in which each half of the respective flange is formed respective halves42 a, 42 b of the valve body 42. The flanges 60, 62, 64 are fully formedwhen the valve body 42 is in the closed state. Note that in somealternative embodiments, the valve body 42 may omit the terminatingflanges 60, 62, 64. In the embodiment of FIG. 5, the valve body 42 isillustrated with two valves 44, 46 that are mounted on the valve body42. Each valve 44, 46 includes an actuator element 66 that passesthrough an opening in the respective valve body half 42 a, 42 b and isselectively actuated to “pinch” an unreinforced polymer conduit 18 thatis disposed inside the passageway of the valve body 42. The valves 44,46 may be any number of types of valves commonly known to those skilledin the art. For example, the valves 44, 46 may be manual valves wherebya bonnet or the like is rotated manually to advance/retract the actuator66. Alternatively, the valves 44, 46 may be automatically actuatedvalves. The valves 44, 46 illustrated in FIG. 5 are pneumaticallyactuated valves using air ports 68, 70. The valves 44, 46 illustrated inFIG. 5 also include an optional position feedback indication switch 72that indicate the position of the valve 44, 46 (e.g., open or closed).The position feedback indication switch 72 may include a port 74 forelectrical cabling.

Still referring to FIG. 5, the valve body 42 (in this embodiment)includes a two-part jacket 76 that includes a first half 76 a and asecond half 76 b that encapsulates the portion of the conduit 18 thatextends beyond the valve body 42. For example, the two-part jacket 76may to cover the conduit segment 48 of FIGS. 4A-4D. The two-part jacket76 is preferably made of a rigid construction using, for example, apolymer based material. Materials include standard thermoplastics andpolyolefins such as polyethylene (PE) and polypropylene (PP) or a hardplastic such as polyetherimide (PEI) such as ULTEM resins. The two-partjacket 76 may also be formed from fluoropolymers such as polyvinylidenefluoride (PVDF) or perfluoroalkoxy (PFA), polytetrafluoroethylene(PTFE), polycarbonate (which may be more thermally resistant),polysulfone (PSU), and the like. The two halves 76 a, 76 b of the jacket76 are connected via hinges 78 that allow the jacket 76 to be opened andclosed as needed. The two-part jacket 78 defines an exoskeleton-typestructure that surrounds the unreinforced polymer conduit 18 andprevents the unreinforced polymer conduit 18 from failing (e.g.,bursting or forming an aneurysm type bulge in the conduit) under highfluid pressures.

In the embodiment of FIG. 5, the ends of the two-part jacket 76 includesflanges 80, 82 that are formed in each half 76 a, 76 b. In thisembodiment, flange 80 is formed to mate with the flange 64 of thetwo-part valve body 42. An optional seal such as an o-ring type seal(not shown) may be placed between the flanges 80, 64 to aid in forming afluid-tight seal. In this configuration, a conventional clamp such asclamp 50 of FIGS. 4B-4D may be positioned about the mated flanges 80, 64to secure the two-part jacket 76 to the two-part valve body 42. Stillreferring to FIG. 5, the unreinforced polymer conduit 18 is illustrateddisposed within the circular-shaped passageway formed in the two-partvalve body 42 and the passageway formed in the two-part jacket 76. Theunreinforced polymer conduit 18 may be made from a polymer thermoplasticelastomers (TPE), thermoplastic rubber (TPR), silicone (thermally orUV-cured), or other polymers.

In one aspect of the invention, the outer diameter of the unreinforcedpolymer conduit 18 is substantially equal to the inner diameters of thepassageways in the valve body 42 and jacket 76. In this regard, both thetwo-part valve body 42 and the two-part jacket 76 snugly encapsulatesthe unreinforced polymer conduit 18 and provides resistance to expansionor other movement of the unreinforced polymer conduit 18 caused by highfluid pressures. As illustrated in FIG. 5, the ends of the unreinforcedpolymer conduit 18 include respective flanges 86, 88, 90 that aredimensioned to fit and reside within the corresponding flanges of thetwo-part valve body 42 and the flange of the two-part jacket 76. Theflanges 86, 88, 90 may be constructed such that an adjacent flange fromanother unreinforced polymer conduit 18 (e.g., segment 48 in FIGS.4A-4D) will mate to form a fluid-tight seal. For example, the flange 86,88, 90 may contain a male sealing ring or extension that fits within acorresponding female recess of another unreinforced polymer conduit 18(or vice versa). The dimensions of the unreinforced polymer conduit 18may vary. The inner diameter of the unreinforced polymer conduit 18 mayrange from ⅛ inch up to 2.5 inches or more.

It should be understood that while many different embodiments arediscussed herein, different embodiments may incorporate features orelements of other embodiments even though there are not specificallymentioned herein. For example, in FIG. 5, the two-part jacket 76 may beomitted or, alternatively, two valve bodies 42, 42′ can be connecteddirectly to one another (without any conduit segment 48) or with othertypes of jackets 76. Moreover, in some embodiments, there are no exposedportions of conduit 18, ′18. Instead, the conduit 18, 18′ isencapsulated within a jacket or other structure. Moreover, while thespecific block-and-bleed valve arrangement of FIGS. 4A-4E isillustrated, the plugs 10, 10′ may be used in any number of differentconfigurations. In addition, while the plugs and other aspects describedherein have largely been described in the context of pharmaceutical orbiologic drug production processes, the plugs may also be used in othersterile processes (e.g., food or dairy production). While embodiments ofthe present invention have been shown and described, variousmodifications may be made without departing from the scope of thepresent invention. The invention, therefore, should not be limited,except to the following claims, and their equivalents.

1. A sterile fluid system comprising: a container for holding fluidtherein; a flexible polymer conduit having first and second ends, theflexible polymer conduit coupled to the container at the first end; aremovable plug configured to insert into the second end of the flexiblepolymer conduit, the removable plug comprising: a cap; a shank portionextending from the cap; a flexible ring disposed along a portion of theshank; and a lever mounted on the cap and configured to shorten theshank upon actuation, wherein actuation of the lever causes radialexpansion of the flexible ring and forms a fluidic seal with an interiorsurface of the flexible polymer conduit, wherein the removable plug isformed form a polymer material that tolerates gamma radiation.
 2. Thesterile fluid system of claim 1, wherein the container comprises a bag.3. The sterile fluid system of claim 1, wherein the container andflexible polymer conduit are formed from a polymer material thattolerate gamma irradiation.
 4. The sterile fluid system of claim 1,wherein the flexible polymer conduit further comprises a third end,wherein the second end comprises a main conduit and the third endcomprises a branch conduit.
 5. The sterile fluid system of claim 4,further comprising a removable plug configured to insert into the thirdend.
 6. A removable plug configured to insert into an end of a flexiblepolymer conduit, the removable plug comprising: a cap; a shank portionextending from the cap; a flexible ring disposed along a portion of theshank; and a lever mounted on the cap and configured to shorten theshank upon actuation, wherein actuation of the lever causes radialexpansion of the flexible ring and forms a fluidic seal with an interiorsurface of the flexible polymer conduit, wherein the removable plug isformed from a polymer material that tolerate gamma irradiation.
 7. Theremovable plug of claim 6, wherein the shank comprises a fixed portionand a moveable portion wherein the flexible ring is interposed betweenthe fixed portion and the moveable portion.
 8. The removable plug ofclaim 7, wherein the lever comprises a cam surface that contacts asurface of the cap.
 9. A method of using the removable plug of claim 6comprising: inserting the shank portion into an end of the flexiblepolymer conduit; actuating the lever, whereby the flexible ring contactsthe interior surface of the flexible polymer conduit.
 10. The method ofclaim 9, further comprising: actuating the lever in a reverse direction;removing the plug from the flexible polymer conduit.
 11. A method ofconnecting a fluid container to a secondary conduit in a sterile mannercomprising: sterilizing the fluid container and a first conduitconnected to the fluid container, wherein the first conduit includes amain conduit and branch conduit and wherein an end of the branch conduitand an end of the main conduit each contain a removable plug therein;securing a first valve body around the main conduit and the branchconduit of the first conduit, wherein the first valve body includes afirst valve for the main conduit and second valve for the branchconduit; closing the first valve of the first valve body and closing thesecond valve of the first valve body; removing the plugs from the branchconduit and main conduit of the first conduit; securing a second valvebody around a secondary conduit, the secondary conduit having a mainconduit and a branch conduit, wherein the second valve body includes afirst valve for the main conduit and second valve for the branch conduitof the secondary conduit; fluidically connecting an output of the mainconduit of the first conduit to the main conduit of the secondaryconduit; opening the second valve of the first valve body and openingthe second valve of the second valve body; flowing a sterilant through afluid pathway connecting between the branch channel of the first conduitand the branch channel of the secondary conduit; closing the secondvalve of the first valve body and closing the second valve of the secondvalve body; and opening the first valve of the first valve body andopening the first valve of the second valve body.
 12. The method ofclaim 11, wherein the first valve body comprises a first half and asecond half hinged with respect to one another, wherein the main conduitand the branch conduit of the first conduit is disposed between thefirst half and the second half.
 13. The method of claim 11, whereinprior to securing the output of the main conduit of the first conduit tothe main conduit of the secondary conduit comprises closing the firstvalve of the second valve body and the second valve of the second valvebody and removing plugs from the main conduit and the branch conduit ofthe secondary conduit.
 14. The method of claim 11, wherein the fluidcontainer comprises a bag.
 15. The method of claim 11, whereinsterilizing comprises irradiating the fluid container, first conduit,and plugs with gamma irradiation.
 16. The method of claim 11, whereinthe sterilant comprises steam, a chemical agent, or ozone.